Reports of deleterious reproductive effects ascribed to the actions of endocrine disrupting chemicals are steadily increasing. One chemical in particular, bisphenol A (BPA), has been the focus of considerable attention and controversy. . BPA is one of the highest volume chemicals in production and humans are exposed to low levels on a daily basis. Recent studies in the mouse indicate that exposure to low levels of BPA during three distinct developmental stages in utero can adversely affect the genetic quality of the egg. Thus, these findings, and those from a host of other rodent studies, raise grave concerns about human fetal exposures. Directly assessing the effects of this chemical in humans, however, is neither ethically nor experimentally feasible. The proposed studies represent the first attempt to use a more relevant animal model, the rhesus monkey, to answer questions about the pharmacokinetics of BPA and to directly assess its effects on the early events of oogenesis in the fetal ovary. The oral dose of BPA used in these studies will be carefully monitored so that the resulting blood levels will be within the range currently found in humans. Aim 1 will test the hypothesis that BPA clearance rates differ in pregnant and non-pregnant female monkeys and that BPA levels accumulate in fetal tissues. Aim 2 will test the effect of BPA exposure on the earliest events of oogenesis in the fetal ovary. The BPA dose will be carefully timed during the pregnancy to coincide with the time of meiotic entry of the fetal oocytes to determine if BPA disrupts the processes of synapsis and recombination between homologous chromosomes. Aim 3 will test the hypothesis that perinatal BPA exposure disrupts follicle formation in the female rhesus monkey. Although BPA exposure has been suggested to induce a variety of effects in experimental animals, to date, no study has measured blood or urine levels of BPA in relation to any health outcome in any species. The combined data from these studies will provide the first direct analysis of the effects of BPA exposure on the developing primate fetus and, as such, will have important implications for humans. PUBLIC HEALTH RELEVANCE: Bisphenol A (BPA) is a widely used compound found in plastics and the lining of cans used for food that has been shown to have deleterious effects on offspring of mice when the pregnant dams are exposed to low doses. This project will measure BPA metabolism in non-pregnant and pregnant monkeys and determine if effects on eggs or ovaries are seen in developing offspring in primates as they are in mice. Because the dose used will be similar to current human blood levels of BPA, the results should have direct relevance to human health. [unreadable] [unreadable] [unreadable]